This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mycobacteria have features that make them attractive as potential HIV-1 vaccine vectors. The attenuated, non-pathogenic mycobacterium bovis BCG is widely used as a vaccine for tuberculosis and leprosy. They can also be readily engineered to stably express transgenes. However, the utility of these vectors has been limited due to the prevalence of pre-existing anti-BCG immunity and poor antigen expression. After developing optimized BCG vectors with enhanced antigen expression, we test the vectors in the AIDS rhesus monkey model in a homologous prime/boost experiment and in a heterologous recombinant BCG/recombinant Adenovirus vector regimen.